2. Academic Validation
  3. B7-H4 (DD-O110) is overexpressed in high risk uterine endometrioid adenocarcinomas and inversely correlated with tumor T-cell infiltration

B7-H4 (DD-O110) is overexpressed in high risk uterine endometrioid adenocarcinomas and inversely correlated with tumor T-cell infiltration

  • Gynecol Oncol. 2007 Jul;106(1):119-27. doi: 10.1016/j.ygyno.2007.03.039.
Takashi Miyatake 1,  Barbara Tringler,  Wenhui Liu,  Shu-Hui Liu,  Jackie Papkoff,  Takayuki Enomoto,  Kathleen C Torkko,  Donna L Dehn,  Ashanta Swisher,  Kenneth R Shroyer
Affiliations

Affiliation

  • 1 Department of Pathology, University of Colorado at Denver and Health Sciences Center, 12800 E.19th Ave. Aurora, CO 80010, USA.
PMID: 17509674 DOI: 10.1016/j.ygyno.2007.03.039
Abstract

Objectives and methods: B7-H4 (DD-O110), a member of the B7 family, negatively regulates T cell-mediated immune response. Previous studies have shown that B7-H4 is highly expressed in endometrioid ovarian cancers with relatively low levels of expression in normal ovary which was confirmed by Western blot. The present study was designed to localize B7-H4 expression by immunohistochemistry (IHC) in normal endometrium, endometrial hyperplasia and uterine endometrioid adenocarcinoma. The pattern of B7-H4 localization was compared with the IHC detection of CD3 and CD8-positive T lymphocytes and CD14 positive macrophages to investigate the role of B7-H4 in the regulation of tumor immune surveillance. B7-H4 expression was evaluated in apoptotic tumor cells.

Results: The proportion and intensity of B7-H4 staining were increased in the progression from normal, hyperplastic and malignant endometrial glandular mucosa. B7-H4 showed a predominantly apical membranous staining (pattern 1) in normal and hyperplastic endometrial epithelium but showed intense circumferential membranous and cytoplasmic staining (pattern 2) in a majority of endometrioid carcinoma cases (p=0.018). The proportion of B7-H4 positive tumor cells and staining intensity was also higher in high risk tumors than in low risk tumors (p=0.001 and p=0.032, respectively). The proportion of B7-H4 positive tumor cells was inversely related to the number of CD3-positive and CD8-positive tumor-associated lymphocytes (TALs). There was a positive correlation between B7-H4 pattern 2 staining and both CD3-positive and CD8-positive tumor-infiltrating lymphocytes (TILs) (p=0.039 and p=0.031, respectively).

Conclusions: B7-H4 is overexpressed in hyperplastic and malignant endometrial epithelium and is correlated with the number T cells associated with the tumor. These results suggest that B7-H4 overexpression may reflect a more aggressive biologic potential and may play a role in tumor immune surveillance mechanisms.

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